Is APOE ε4 associated with cognitive performance in early MS?
Sinah Engel1, Christiane Graetz1, Anke Salmen1
1From the Department of Neurology and Focus Program Translational Neuroscience (FTN) (S.E., C.G., M.M., S.B., S.G., F.Z., C.M.L., F.L.), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (A.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology (A.S., B.A., R.G.), St. Josef-Hospital, Ruhr-University Bochum; Institute of Medical Biostatistics (G.T.), Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz; Department of Neurology (A. Bayas), Klinikum Augsburg; Department of Neurology (A. Berthele, B.H.), Klinikum rechts der Isar, Technical University of Munich; Institut für Neuroimmunologie und Multiple Sklerose (C.H.), Universitätsklinikum Hamburg-Eppendorf; Clinic of Neurology (L.K., S.G.M., H.W.), University Hospital Münster, Westphalian-Wilhelms-University Münster; Institute of Clinical Neuroimmunology (T.K.), Ludwig Maximilian University of Munich; Department of Neurology (R.A.L.), University Hospital Erlangen; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F.P.), Charité - Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.S.), Hannover Medical School; Department of Neurology (B.T.), Philipps-University Marburg; Department of Neurology (F.T.B.), University of Leipzig; Department of Neurology (H.T.), University of Ulm; Clinic of Neurology Dietenbronn (H.T.), Schwendi; Neurology (F.W.), Max-Planck-Institute of Psychiatry, Munich; Neurological Clinic (F.W.), Sana Kliniken des Landkreises Cham; Department of Neurology (B.W.), University of Heidelberg; Department. of Neurology (U.K.Z.), University of Rostock; Central Information Office (CIO) (G.A.), Philipps-University Marburg; and Genetic and Molecular Epidemiology Group (C.M.L.), Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Germany.
APOE ε4 homozygosity impacts cognitive performance in early multiple sclerosis (MS). Higher disability and MRI lesions also reduce cognition, while alcohol consumption may improve scores.
Area of Science:
- Neuroimmunology
- Genetics
- Cognitive Neuroscience
Background:
- Cognitive impairment is common in early multiple sclerosis (MS).
- The apolipoprotein E (APOE) gene, particularly the ε4 allele, is implicated in cognitive function and neurodegenerative diseases.
- Understanding genetic influences like APOE is crucial for predicting cognitive trajectories in MS.
Purpose of the Study:
- To investigate the association between APOE polymorphisms and cognitive performance in patients with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS).
- To identify genetic and clinical factors influencing cognition in early MS.
Main Methods:
- A multicenter cohort study of 552 untreated CIS/RRMS patients.
- Assessed APOE single nucleotide polymorphisms (rs429358 and rs7412) using allelic discrimination assays.
- Evaluated cognitive performance with the 3-second paced auditory serial addition test and the Multiple Sclerosis Inventory Cognition (MUSIC), analyzed using multiple linear regression.
Main Results:
- APOE ε4 homozygosity was linked to lower overall cognitive performance.
- Higher disability levels, MRI lesion load, and depressive symptoms correlated with reduced cognitive function.
- Alcohol consumption was associated with higher cognitive test scores, particularly in memory-related functions.
Conclusions:
- APOE ε4 homozygosity is a potential predictor of cognitive performance in early MS, alongside disease burden indicators.
- Clinical factors like disability and MRI findings significantly impact cognition.
- Lifestyle factors such as alcohol consumption may play a modulatory role in cognitive outcomes.
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